A Registry Based Randomized-Controlled Trial of an Upper Limb Exergaming Intervention for Children and Adolescents With Spinal Muscular Atrophy

Spinal Muscular Atrophy Clinical Trial

— INFORM SMA  

Official title:

A Registry-Based Parallel Group Randomized-Controlled Trial of an Upper Limb Exergaming Intervention for Children and Adolescents With Spinal Muscular Atrophy, With an Optional Open-Label Extension

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06396325
• Other study ID #: MP-37-2022-7289
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: May 2024
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: Mbaye Ndiaye
• Phone: 5149341934
• Email: mbaye.ndiaye[@]muhc.mcgill.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We aim to conduct a randomized registry-based waitlist-controlled trial (RCT) with 22 youth with Spinal Muscular Atrophy (SMA) aged 8-18 years to determine if Tales from the Magic Keep is more effective than usual care for improving occupational performance and satisfaction. This clinical trial is embedded in INFORM RARE, an innovative clinical trials network funded by the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR), co-designed by patients and families, healthcare providers, policymakers, methodologists, and research ethicists (https://www.informrare.ca/). INFORM RARE addresses a recognized need for innovation in treatable pediatric rare diseases to facilitate timely and robust evidence generation in support of knowledge user decision-making. Finally, the study is co-designed by adolescents with SMA and their families, healthcare providers, policymakers, and methodologists, incorporating the SPOR guiding principles of patient engagement at all levels of research.

Description:

METHODS AND ANALYSIS Aims and hypotheses This multisite RCT will be conducted across participating sites of the Registry to determine if the exergame Tales from the Magic Keep is more effective than usual care for improving occupational performance and satisfaction. Secondary outcomes will determine the effects of this exergame compared to usual care on fatigue, daily activities, motor activity, and motor function immediately post-intervention at 8 weeks and post-baseline at 16 weeks following open-label extension for an additional 8 weeks.

Primary hypothesis For youth with SMA aged 8-18 years, Tales from the Magic Keep will be more effective than usual care immediately post-intervention at 8 weeks in improving performance and satisfaction scores on the Canadian Occupational Performance Measure (COPM) by at least a clinically meaningful difference of two points.24 Secondary hypotheses

For youth with SMA aged 8-18 years, Tales from the Magic Keep will be more effective than a waitlist control group receiving usual care immediately post-intervention at 8 weeks:

1. Reducing fatigue as measured on the Patient-Reported Outcomes Measurement Information System (PROMIS-SF).

2. Improving independence in activities of daily living as measured on the SMA Independence Scale (SMAIS).

3. Improving the peak motor activity as measured by upper limb outputs from the Syde.

Furthermore, we hypothesize that in youth with SMA aged 8-18 years, using a construct approach of treatment response based on the COPM immediately post-intervention at 8 weeks and at 16 weeks post baseline:

4. The Total Functional Workspace computed by Kinect will be more responsive to change compared to the change in Revised Upper Limb Module (RULM).

5. The Syde® digital endpoints of change in 99th percentile upper limb rotational effort and 99th percentile vertical wrist acceleration will be more responsive to change compared to the change in RULM.

Trial Design This is a registry-based, multisite parallel waitlist randomized trial. Participants with SMA on Disease Modifying Therapies (DMT) will be randomized to one of two arms: exergaming intervention and usual care or waitlist usual care alone. Usual care will be defined as following the established consensus care guidelines. The planned dosing of the intervention is a minimum of 20 minutes, 3 times per week over 8 weeks (8 total hours). An 8-week period was chosen to reflect typical intervention blocks offered in rehabilitation to strengthen motor performance. The feasibility of a home-based rehabilitation program over this period has been demonstrated in SMA. 26 A 20-minute session was chosen to minimize the potential for fatigability in youth with SMA. The primary outcome is measured immediately post-intervention at 8 weeks; participants in the waitlist control group will then have an opportunity to access the exergame during the open-label phase, giving all participants an opportunity to play. This design was informed by patient preferences and offers a primary timepoint of randomized comparison points. This study protocol is reported using the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) - the SPIRIT-Outcomes 2022 Extension27 and will be registered on clinicaltrials.gov before initiating enrolment.

Recruitment Youth with SMA meeting eligibility criteria will be invited to join the study through our collaborating sites in British Columbia, Alberta, Ontario, Quebec, and Nova Scotia. Sites will begin recruiting once local ethics approval and contract agreements have been obtained. Participant-centred information materials, including video demonstrations of the exergame intervention, have been developed and will be made accessible to support families and youth in learning about the study.

Inclusion criteria

You must meet the following eligibility criteria prior to randomization:

1) Confirmed genetic diagnosis of 5q SMA; 2) Aged 8-18 years old; 3) Able to stay seated independently without support for at least 10 seconds; 4) A score of at least 2 points in entry item A of the RULM (i.e., "Can raise 1 or 2 hands to the mouth but cannot raise a 200 g weight in it to the mouth"); 5) Treated with disease-modifying therapy and 5) Provide consent.

You will be excluded if they meet any of the following criteria: 1) Inability to comply with study procedures according to the site investigator, 2) Severe scoliosis or contractures that would interfere with gameplay or with successful completion of functional assessments, as confirmed by the clinical evaluator, and 3) planned orthopedic surgery 6 months prior to or throughout intervention and follow-up period. There are no exclusion criteria related to feeding support, use of non-invasive ventilation or SMN2 copy number.

Random allocation and blinding Randomization will occur with a 1:1 allocation ratio for patients: intervention group (receiving exergaming intervention) or waitlist control group (continuing with usual care, including any regularly accessed physical activities and rehabilitation services). To ensure effective randomization and allocation concealment, we will use a web-based randomization system maintained at the Ottawa Hospital Research Institute. The allocation sequence will be computer-generated using randomly permuted blocks of variable length, concealed from investigators and research staff.

Blinding of trial participants and treating clinicians to intervention allocation will not be feasible due to the nature of the interventions to be compared. Blinding of outcome assessors for the primary outcome (COPM) is not possible as it is self-reported goals supported by the therapist, who will build on identified goals throughout the weekly virtual meetings. Caregivers and you will be blinded to previous COPM scores. The data scientists computing Syde® digital endpoints will be blinded to the treatment arm by providing them only with study ID and raw Syde output to reduce the risk of biased outcome ascertainment. The data scientists computing the Kinect data will be blinded to the treatment period (A or B). Furthermore, data analysts will be blinded to the treatment group by providing them with the data as groups A and B.

Intervention The exergaming intervention is Tales from the Magic Keep, developed in consultation with patient partners, clinicians and F. Hoffmann-La Roche Ltd to target upper limbs and trunk movement in youth with SMA. The dosing will consist of three weekly sessions at home of 20 minutes over 8 weeks. One in-person calibration and an optional recalibration will be performed at the study site.

Patient partners and the INFORM RARE youth advisory group provided input on exergame content and integrated game incentives, a measure we anticipate will facilitate adherence to the exergaming intervention. The game uses a narrative design, shown to be more efficient in sustaining interest and adherence. It includes successively challenging missions and within-game rewards. Potential participants can view user-centred information materials, including video demonstrations of exergame interaction, providing detailed information about the game to elicit interest in participation and inform study participation decisions. You will receive weekly virtual check-ins with the study physiotherapist/research coordinator for troubleshooting and motivational purposes. Adherence will be both self-reported using a gameplay tracking form and captured digitally directly from the Kinect sensor. Monthly meetings will be organized between trainers of all sites for troubleshooting

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 18 Years

Eligibility

Inclusion Criteria:

• Confirmed genetic diagnosis of 5q SMA

• Age at screening: Aged 8-18 years old

• Participant is able to stay seated independently without support for at least 10 seconds

• Participants has a score of at least 2 points in entry item A of the RULM (i.e., "Can raise 1 or 2 hands to the mouth but cannot raise a 200 g weight in it to the mouth")

• Treated with disease-modifying therapy

• Signed ICF

Exclusion Criteria:

• Inability to comply with study procedures according to the site investigator

• Severe scoliosis or contractures that would interfere with gameplay or with successful completion of functional assessments, as confirmed by the clinical evaluator

• Planned orthopedic surgery 6 months prior to or throughout intervention and follow-up period

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Other:
• Exergaming
Play the exergame a minimum of three times a week for 20 minutes over 8 weeks (8 hours total)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Canadian Occupational Performance Measure (COPM)	Primary outcome; The COPM is a validated, widely used tool in pediatric neuromotor disorder research that reliably captures individual occupational performance in self-care, leisure and productivity and has been used in studies of adults with SMA and youth with neuromotor disorders. COPM is a patient-reported outcome measure used to identify and prioritize challenges restricting youth's participation in daily activities. This measure is obtained by semi-structured interviews with the child and their caregiver and focuses on occupational performance in all areas of life, identifying challenges in self-care, leisure, and productivity. The COPM has been used as a primary outcome measure in clinical trials for youth with disabilities, where test-retest reliability is consistently above the acceptable range. Feasibility in the SMA population has been demonstrated.	16 hours
Secondary	Upper limb motor activity	Upper limb motor activity: Wearable devices can capture objective changes in daily activity in the patient's home and community settings. We will implement real-time monitoring using Syde® (Sysnav, France), a class 2 medical wearable device specifically designed for neuromuscular disorders. The Syde® platform includes two wearable sensors for precise movement capture, a back-end IT platform with algorithms for digital endpoint calculations, and services for clinical operations. The sensor is composed of a tri-axial accelerometer, a gyroscope and a magnetometer, providing an objective measure of physical activity obtained from the patient's performance of daily activities in their usual environment	16 hours